The objectives of the proposed studies are to determine the major factors which control or regulate insulin and glucagon secretion by the islet cells of the pancreas. Studies planned include: (1) the effects of guanine nucleotides on insulin and glucagon secretion, (2) the interaction of prostaglandins and adenyl cyclase in isolated pancreatic islets, (3) the effects of different hormones and neurotransmitters on release of insulin and glucagon by pancreatic islet cells grown in culture, (4) morphologic and biochemical studies of pancreatic endocrine function following chemical sympathectomy with 6-hydroxydopamine in dogs. The results of this work may provide important information necessary for understanding the causes and treatment of diabetes mellitus and islet cell tumors.